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J P Thomas

Publications and source records attributed to J P Thomas.

At least 19 recordsLinked to original sources

Configural effects constrain Fourier models of pattern discrimination.

Many models of spatial pattern discrimination assume that judgments are based on information directly available from mechanisms tuned to limited ranges of spatial frequency and orientation. We tested the validity of this assumption for spatial frequency, orientation, and contrast information in a series of complex pattern discrimination experiments. Observers discriminated between simple gratings, between gratings masked by components that differed widely in spatial frequency and/or orientation, and between patterns that presented two cues to discrimination, one in each frequency and/or orientation band. Component cues were combined either in rigid-object correspondence (e.g. both components were rotated clockwise in one pattern and counterclockwise in the other) or in opposition (e.g. in one pattern one component was rotated clockwise, the other counterclockwise; the direction of rotation was reversed for each component in the second pattern). The results demonstrate that information from tuned pathways is not always used directly in making spatial judgments, but in some cases is combined across wide regions of the Fourier domain prior to the discrimination decision. We find two distinct patterns of combination that appear to independently signal information about texture and edges. These findings provide a potential link between low-level, spatially tuned analyzers in the visual system and higher-level pattern processing mechanisms.

Adult

Using distinctive Fourier components to discriminate between complex patterns.

Observers discriminated between a plaid pattern formed by summing vertical and horizontal cosine gratings, and a plaid formed by multiplying the gratings. Such patterns are alike with respect to many non-Fourier primitives, but differ in the Fourier domain by diagonal components which are present in the plaid formed by multiplication, but not in the one formed by summing. When discrimination performance is related to the contrast of the diagonal components, it is found that the contrast threshold for discrimination is approximately the same as the threshold for detection of the isolated components. However, the psychometric function for discrimination is shallower than that for detection, suggesting the presence of masking. Despite the masking, the results support the proposition that discrimination processes may operate directly on the representations of local Fourier components.

Contrast Sensitivity

Effect of pattern adaptation on spatial frequency discrimination.

The effect of pattern adaptation on spatial frequency discrimination was examined in two experiments. In the first experiment delta f/f was measured (with and without adaptation) as a function of stimulus contrast; in the second experiment the contrast required to discriminate a fixed delta f/f was measured (with and without adaptation) as a function of the value of delta f/f. Maximum precision, as measured by the asymptotic value that delta f/f approaches at medium and high contrasts, was not altered by adaptation. Rather, the effect of adaptation was to translate the functions relating delta f/f and contrast along the log-contrast axis, i.e., to increase by a constant factor the contrast required to achieve a given precision of discrimination. This factor agreed closely with the factor by which adaptation raised the contrast threshold for detection of the test stimuli. The largest effects were observed when the reference and the adapting stimuli had the same spatial frequency (5 cycles/deg). Smaller or negligible effects were observed when reference and adapting frequencies differed by an octave.

Adaptation, Ocular

Lethal damage to murine L1210 cells by exogenous lipid hydroperoxides: protective role of glutathione-dependent selenoperoxidases.

The effect of selenium deprivation on the viability of murine L1210 cells exposed to various exogenous lipid hydroperoxides has been investigated. Selenoperoxidase activities of cells grown for longer than 1 week in 1% serum with no added selenium [Se(-) cells] were less than 10% of the activities of selenium-satisfied controls [Se(+) cells] or selenium-repleted counterparts [Se(-/+) cells]. The enzymes measured were classical glutathione peroxidase (GPX) and phospholipid hydroperoxide glutathione peroxidase (PHGPX). Se(-) cells exhibited a compensatory increase in catalase activity. Dye exclusion and clonal survival assays indicated that Se(-) and Se(+) cells were relatively insensitive to photochemically generated phospholipid hydroperoxides in liposomal form. However, both cell types were sensitive to liposomal cholesterol hydroperoxides, e.g., 7-hydroperoxycholesterol (7-OOH), Se(-) being much more so (LD50 approximately 10 microM) than Se(+) (LD50 approximately 75 microM). By contrast, 7-hydroxycholesterol over a comparable concentration range was minimally toxic to Se(-) and Se(+) cells. Cell killing by 7-OOH was inhibited by desferrioxamine and by butylated hydroxytoluene, suggesting that iron-mediated free radical reactions are involved. The involvement of glutathione in cytoprotection was confirmed by showing that Se(+) cells were more sensitive to 7-OOH after treating with buthionine sulfoximine, an inhibitor of GSH synthesis. Cellular detoxification of 7-OOH is provisionally attributed to PHGPX rather than GPX, since 7-OOH and other cholesterol hydroperoxides were found to be good substrates for PHGPX in a cell free system, but were unreactive with GPX.

Animals

When orthogonal orientations are not processed independently.

We studied the extent to which two gratings, superimposed at orthogonal orientations, are processed independently in making spatial frequency discriminations. Our findings suggest that independence is not preserved in this task, and that it breaks down in two distinct ways: (1) judgments about one component are reduced in accuracy by the presence of the second; and (2) information about the two component gratings is not used independently in making judgments about the compound stimulus formed by them. These results place constraints on the applicability of models that assume information from spatially tuned mechanisms is directly available in performing a discrimination task.

Cues

Non-secretory adenomas of the pituitary treated by trans-ethmoidal sellotomy.

A consecutive series of 35 clinically non-secretory pituitary adenomas treated surgically by the transethmodial approach is presented. Mean age at presentation was 60 years, with a male-to-female ratio of 2:1. These tumours present later than hormone secreting tumours: 90% were over 2 cm in diameter at operation. Seventy-one per cent of patients had impaired vision and 89% had hypopituitarism. Surgical treatment relieved or significantly improved visual fields in 79% of patients with impaired vision. Ninety-one per cent required permanent hormone replacement. Mean follow-up was for 4.4 years. Five tumours recurred, causing recurrent visual symptoms. No tumours recurred in those patients treated with postoperative radiotherapy, but follow-up in this group was only for a mean of 2.7 years.

Adenoma

Reactivity of phospholipid hydroperoxide glutathione peroxidase with membrane and lipoprotein lipid hydroperoxides.

A comparative study has been carried out on the general reactivity of lipid hydroperoxides in liposomes, biological membranes and lipoproteins with two Se-dependent peroxidases: Glutathione Peroxidase (GPX) and Phospholipid Hydroperoxide Glutathione Peroxidase (PHGPX). While PHGPX reduces all hydroperoxides derived from phospholipids, cholesterol and cholesterol esters, GPX reduces only fatty acid hydroperoxides released after treatment of phospholipid hydroperoxides with phospholipase A2. These findings highlight the role of PHGPX in protecting biomembranes from peroxidative damage and add new insight into how cholesterol hydroperoxides are detossified in cells.

Cholesterol

Enzymatic reduction of phospholipid and cholesterol hydroperoxides in artificial bilayers and lipoproteins.

Lipid hydroperoxides (LOOHs) in various lipid assemblies are shown to be efficiently reduced and deactivated by phospholipid hydroperoxide glutathione peroxidase (PHGPX), the second selenoperoxidase to be identified and characterized. Coupled spectrophotometric analyses in the presence of NADPH, glutathione (GSH), glutathione reductase and Triton X-100 indicated that photochemically generated LOOHs in small unilamellar liposomes are substrates for PHGPX, but not for the classical glutathione peroxidase (GPX). PHGPX was found to be reactive with cholesterol hydroperoxides as well as phospholipid hydroperoxides. Kinetic iodometric analyses during GSH/PHGPX treatment of photoperoxidized liposomes indicated a rapid decay of total LOOH to a residual level of 35-40%; addition of Triton X-100 allowed the reaction to go to completion. The non-reactive LOOHs in intact liposomes were shown to be inaccessible groups on the inner membrane face. In the presence of iron and ascorbate, photoperoxidized liposomes underwent a burst of thiobarbituric acid-detectable lipid peroxidation which could be inhibited by prior GSH/PHGPX treatment, but not by GSH/GPX treatment. Additional experiments indicated that hydroperoxides of phosphatidylcholine, cholesterol and cholesteryl esters in low-density lipoprotein are also good substrates for PHGPX. An important role of PHGPX in cellular detoxification of a wide variety of LOOHs in membranes and internalized lipoproteins is suggested from these findings.

Cholesterol

Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides.

The general reactivity of membrane lipid hydroperoxides (LOOHs) with the selenoenzyme phospholipid hydroperoxide glutathione peroxidase (PHGPX) has been investigated. When human erythrocyte ghosts (lipid content: 60 wt % phospholipid; 25 wt % cholesterol) were treated with GSH/PHGPX subsequent to rose bengal-sensitized photoperoxidation, iodometrically measured LOOHs were totally reduced to alcohols. Similar treatment with the classic glutathione peroxidase (GPX) produced no effect unless the peroxidized membranes were preincubated with phospholipase A2 (PLA2). However, under these conditions, no more than approximately 60% of the LOOH was reduced; introduction of PHGPX brought the reaction to completion. Thin layer chromatographic analyses revealed that the GPX-resistant (but PHGPX-reactive) LOOH was cholesterol hydroperoxide (ChOOH) consisting mainly of the 5 alpha (singlet oxygen-derived) product. Membrane ChOOHs were reduced by GSH/PHGPX to species that comigrated with borohydride reduction products (diols). Sensitive quantitation of PHGPX-catalyzed ChOOH reduction was accomplished by using [14C]cholesterol-labeled ghosts. Kinetic analyses indicated that the rate of ChOOH decay was approximately 1/6 that of phospholipid hydroperoxide decay. Photooxidized ghosts underwent a large burst of free radical-mediated lipid peroxidation when incubation with ascorbate/iron or xanthine/xanthine oxidase/iron. These reactions were only partially inhibited by PLA2/GSH/GPX treatment, but totally inhibited by GSH/PHGPX treatment, consistent with complete elimination of LOOHs in the latter case. These findings provide important clues as to how ChOOHs are detoxified in cells and add new insights into PHGPX's protective role.

Animals

Cue summation in spatial discriminations.

We investigated the extent to which discrimination performance improves when more than a single cue distinguishes two patterns. When two simple gratings differ slightly in spatial frequency, orientation, and/or contrast, the performance of most observers is better in multiple-cue conditions than in single-cue conditions and by an amount indicating Euclidean summation of information. These results are shown to be consistent with discrimination models that integrate information over different, spatially selective pathways. However, little summation is found when the task requires integration of cues across widely separated spatial frequency bands. This result implies that information is integrated only over pathways tuned to a common region of the spatial frequency domain.

Contrast Sensitivity

Common deficiencies of NIDRR research applications.

The purpose of this article was to identify and describe those deficiencies determined by nonfederal peer reviewers during the most recent 1989 NIDRR research competition to mitigate successful funding support from the lead federal agency concerned with medical rehabilitation research. In 1989, 232 field investigator-initiated research applications were received in response to the Federal Register announcement of September 8, 1988. Of these, 57 or 24.5% were assigned to the Medical Sciences Programs office. Six applications were ultimately approved and funded (10.7%). The remaining 51 (89.5%) were statistically analyzed to determine deficiencies significant in warranting disapproval. The 51 applications averaged 5.68 deficiencies each. Five types of research error accounted for 76.8% of all deficiencies noted by reviewers. These included methodologic errors (25) and inadequate control of subject variables (25), followed by inappropriate research design (24), poor conceptualization of problem/approach (21) and incorrect statistical analysis (14). The top ranked singular deficiency was poor conceptualization of problems or approach. Other flaws warranting lowering of potential scores by reviewers included excessive budget requests, duplication of effort with on-going supported research, inadequate background of investigator and weak dissemination and utilization plans. In conclusion, many applications are submitted for the NIDRR field investigator-initiated research program competitions that are significantly deficient. Those identified areas of deficiency cover most oF the conceptualization, research design and methodologic criteria essential for valid, creditable scientific investigation.(ABSTRACT TRUNCATED AT 250 WORDS)

Government Agencies

Postnatal development of the middle ear: areal ratios in kittens.

Developmental changes in tympanic membrane to stapedial footplate areal ratios were investigated in kittens from birth through the twentieth postnatal day. Measurements from 45 kittens (85 temporal bones) were obtained from the pars tensa region of the tympanic membrane and the stapedial footplate region bounded by the annular ligament using standard macrophotographic and computer digitization techniques. Tympanic membrane and stapedial footplate areas were approximately 70% and 80%, respectively, of their adult size at birth and relevant areas increased exponentially during early postnatal life. Adultlike dimensions were achieved by the end of the first postnatal week. Tympanic membrane:stapedial footplate areal ratios increased from approximately 25:1 to 30:1 during the first postnatal week, before the developmental period during which adultlike auditory thresholds and response amplitudes are acquired. Thus, the areal ratio influences on impedance-matching characteristics of the middle ear do not appear to significantly affect the postnatal development of auditory function in cats.

Animals

Role of lipid peroxidation in hematoporphyrin derivative-sensitized photokilling of tumor cells: protective effects of glutathione peroxidase.

The ability of cells to detoxify lipid hydroperoxides (LOOHs) generated by hematoporphyrin derivative (HPD)-sensitized photooxidation was investigated for the first time. The general importance of glutathione in cytoprotection was confirmed by showing that murine L1210 cells were more sensitive to the lethal effects of HPD plus red light after being treated with buthionine sulfoximine. The specific role of Se-dependent glutathione peroxidase was investigated by using L1210 cells that were grown in Se-deficient media. Glutathione peroxidase activity of such cells was typically less than 5% of that exhibited by Se-replete cells. When examined by means of dye exclusion or clonogenic assay, Se-deficient cells were dramatically more sensitive to HPD-mediated photokilling than normal counterparts. Impaired metabolism of hydrogen peroxide was ruled out as a possible cause of enhanced photokilling, since added catalase had no protective effect on Se-deficient cells. Iodometric analysis of lipid extracts from photooxidized cells indicated a significantly greater rate of LOOH accumulation as a result of Se depletion. Moreover, when depleted cells were incubated in the dark after a short period of photo-peroxidation, LOOH decay was markedly slower than in controls. Similar results were obtained with human CaSki cells derived from cervical carcinoma. It is apparent from these results that lipid peroxidation plays an important role in tumor cell eradication by HPD/phototherapy, and that glutathione peroxidase serves as a natural protectant against photokilling by catalyzing the reduction of LOOHs.

Animals

A new family of water-soluble, third generation antitumor platinum complexes.

[1,1-Cyclobutanedicarboxylato(2)-O,O'](1,3-dioxane-5,5-dimethan amine- N,N')platinum(II), 3a, a third generation, very water-soluble platinum complex, has been synthesized along with several of its analogues. All members of the new family contain a 1,3-dioxane or 1,3-dioxolane-1,3-diamine as their basic ligand, a moiety which contributes to their increased water solubility, and a bidentate acid ligand, which is responsible for their good stability. They were all easily crystallized and characterized by 1H NMR and elemental analysis, and the parent complex 3a was further characterized by 13C NMR. Their very desirable physical properties combined with their broad spectrum of antitumor activity and reduced toxicity make them good candidates of further development.

Animals

Reactivity of photochemically-generated lipid hydroperoxides in cell membranes with glutathione peroxidase.

The ability of glutathione peroxidase (Gpx) to catalyze the reductive inactivation of photochemically-generated lipid hydroperoxides (LOOHs) was investigated, using hematoporphyrin derivative (HPD) as a photosensitizing agent and erythrocyte ghosts as membrane targets. Glutathione peroxidase was reactive toward photoperoxidized membranes only after their exposure to phospholipase A2 (PLA2). Iodometrically-determined LOOH values were typically 30-40% greater than values measured by enzymatic assay using Gpx and glutathione reductase. A consistent result was obtained when photooxidized membranes were treated with PLA2 and GSH/Gpx followed by iodometric assay, viz. persistence of approximately 40% of the starting LOOH. Whereas photooxidized egg phosphatidylcholine liposomes underwent total LOOH loss when incubated with PLA2 and GSH/Gpx, no net loss was observed with photooxidized cholesterol/dimyristoyl-phosphatidylcholine liposomes. The results suggest that cholesterol hydroperoxides in ghost membranes account for the Gpx-resistant fraction of LOOHs.

Erythrocyte Membrane